The effects of ethanol exposure on mammalian central nervous system function will be pursued using both extracellular and intracellular recording in the intact brain in situ, in the in vitro brain slice and in intraocular brain transplants. Studies will focus on genetic variants manifesting differential alcohol-related behaviors as model systems for examining acute ethanol actions as well as for studying tolerance and dependence to alcohol. The long-term objectives of this research program are three fold. First, the mechanism of electrophysiological responses to ethanol will be characterized as direct, modulatory or involving local circuit interneurons. Second, changes in responses to ethanol, as well as functional changes in neurotransmitter systems will be determined after induction of tolerance or dependence. Finally, the genetic variants will permit ethanol-induced electrophysiological responses to be correlated with alcohol-induced behaviors. A greater understanding of how ethanol alters CNS function should furnish new insights into the problems of alcohol intoxication and alcoholism.